Pulmonary arterial hypertension

Question 1

Diagnosis of PAH?

Answer 1

Right heart catherisation

PAPm>25 = PAH

PASP >15 = PH due to cardiac disease
PASP <15 = either:
 - PAH
 - PH secondary to lung disease
 - Chronic thromboembolic PH
 - PH of unknown cause

Question 2

Should we screen for PAH in high risk groups?

Connective tissue disease - esp. scleroderma
HIV
Hereditary PAH

Answer 2

Yes

Improves prognosis

Question 3

Gene mutation for PAH 1

Answer 3

BMPR

Found in 40% of idiopathic PAH
Inhibits smooth muscle proliferation and induces apoptosis –> vascular remodelling

Question 4

Poor prognostic factors?

Answer 4

Male
Connective tissue disease
Older age
Worse NYHA class

Question 5

Pathogenesis of PA

Answer 5

Vasoconstriction 2ndary to endothelial dysfunction
Endothelial dysfunction –> chronic decrease in NO and prostacyclin and increase in endothelin 1

Results in remodelling –> increased endothelial and SM cells –> disordered angiogenesis

Results in thrombosis in situ

Question 6

What is the role of endothelin 1 in PAH -1

Answer 6

Potent vasoconstrictor
Stimulates proliferation of smooth muscle

Levels correlate with disease activity and mortality

Question 7

General treatment of PAH?

Answer 7

Treat the underlying disease !!!
Pulmonary rehabilitation
O2 if hypoxic
Anticoagulation for PAH 1 and 4

Question 8

Treatment for PAH-1

Answer 8

CCBs –> improved mortality in idiopathic PAH

Warfarin

Prostaglandins

Endothelin receptor antagonists

PDE5 inhibitors

Riociguat

Lung transplant

Question 9

Prostaglandins

Answer 9

Prostaglandin = increased cAMP –> vasodilation and antiproliferation

Epoprostenol
IV = CVC
Inhibits platelet aggregation
MORTALITY BENEFIT
S/Es: Jaw pain, arthralgia and diarrhoea

Treprostinil =s/c nil mortality benefit
Illoprost = inhaled = nil mortality benefit

SELEXIPEG = oral selective prostacycline receptor agonist - improved morbidity/mortality

Question 10

Endothelin receptor antagonist

Answer 10

Prevents vasoconstriction

Bosentan = Endothelin A and B receptor antagonist
–> hepatotoxicity

Ambrisenten = Endothelin A receptor antagonist
? worsens symptoms ILD in patients with IPF

Macitenten = Endothelin A and B receptor antagonist
Nasopharyngitis and anaemia
Improves morbidity/mortality

Question 11

PDE5 inhibitors

Answer 11

Increases intracellular cAMP and cGMP –> vasodilatation

Sildenafil , Tadalafil, Vardenafil

Improves symptoms

Question 12

Riociguat

Answer 12

Stimulates soluble guanylate cyclase –> stimulates NO receptor and increases the sensitivity of sGC to endogenous NO

Improves symptoms in PAH 1 and 4